Telomerase activity is tightly regulated during T cell development, differentiation, and activation. In peripheral blood resting T cells, telomerase activity is low to undetectable despite both telomerase components (TERT and TER) are expressed. Recently, it has been reported that alternate splicing of TERT negatively regulates telomerase activity, as the alternative splicing products of TERT resulted from frame shift or early termination of translation. To determine whether the alternative splicing of TERT is the reason for the low to undetectable level of telomerase activity in T cells, we applied single cell RT-PCR method and found that the majority of resting T cells express mRNA without alternative splicing. Thus, the regulation of telomerase activity in resting T cells may be due to other mechanisms, such as posttranslational modifications. In the study of non-telomere lengthening function of telomerase, we have found that telomerase activity is associated with the survival of human CD4 T cells under homeostatic cytokine (IL-7) in vitro. Currently, we used telomerase knockout mice of TERT and TER to directly address if TERT or TER or telomerase is required for the homeostatic cytokine, IL-7, medicated proliferation and survival of T cells.